There is growing clinical interest in the use of 125I (half-life 59.4 days) and 103Pd (half-life 16.97 days) for permanent brachytherapy implants. These radionuclides pose interesting radiobiological challenges because, even with slowly growing tumours, significant tumour cell repopulation may occur during the long period taken to deliver the full radiation dose. This results in a considerable amount of the prescribed dose being wasted. There may also be changes in the tumour volume during treatment (due to oedema and/or shrinkage), thus altering the relative geometry of the implanted seeds and causing additional dose rate variations. This assessment examines the interaction between the above effects and additionally includes allowance for the influence of the relative biological effectiveness (RBE) of the radiations emitted by the two radionuclides. The results are presented in terms of the biologically effective doses (BEDs) and likely tumour control probabilities (TCPs) associated with the various parameter combinations. The overall BED enhancement due to the RBE effect is shown always to be greater than the RBE itself and is greatest in tumours which are radio-resistive and/or fast growing. The biological dose uncertainties are found to be less with 103Pd and the TCPs associated with this radionuclide are expected to be significantly higher in the treatment of some 'difficult' tumours. Using typically prescribed doses 125i appears to be better for treating radiosensitive tumours with long doubling times and which shrink fairly rapidly. However, unless 125I doses are reduced, this advantage may well be offset by the greatly enhanced biological doses delivered to adjacent normal structures.
A tumour shrinkage factor is incorporated into previously derived linear-quadratic (LQ) formulae which allowed radiobiological assessment of the efficacy of permanently implanted radionuclides. The new formulations relate the biologically effective dose (BED) to radionuclide half-life, recovery half-life, tumour radiosensitivity, potential doubling time and linear shrinkage rate. Specific attention has been given to the following radionuclides: gold-198 (half-life, 2.7 days), palladium-103 (half-life, 17 days), ytterbium-169 (half-life, 32 days) and iodine-125 (half-life, 60 days). For each nuclide the log cell kill resulting from typically prescribed doses was calculated for a range of tumour clonogen doubling times at various radiosensitivities and linear shrinkage rates. It is shown that even relatively modest shrinkage rates are capable of enhancing the clinical potential of the longer-lived nuclides. However, even though the effect of tumour shrinkage is minimal in the case of gold-198, for fast growing and/or insensitive tumours there are fewer radiobiological uncertainties associated with the use of this nuclide. The revised equations may also have applications in certain types of biologically targeted radiotherapy.
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